INTRODUCTION:

Hey all you smart nurses out there! I wonder if anyone had any experience with this rare autoimmune disease. It's an autoimmune disorder that usually "attacks" the lungs or kidneys. It deposits granulomas, or crystal-like deposits into the tissues or any body organs. As an Associate Professor in a college of Nursing, my role is to teach and supervise the nursing students in the clinical areas and to take part in the clinical teaching.

Recently a patient who is a known case of Wagner’s granulomatosis made me realize that he demand good medical and continuous nursing care. He was admitted with respiratory infection and breathlessness, flitting arthritis, scleritis and his blood reports showed his ESR and CRP was high and ANCA (anti-neutrophil cytoplasmic antibody) test strongly positive.

GPA has a spectrum of clinical presentations that includes recurrent respiratory infection in adults and upper and lower respiratory tract problems in children. In addition, patients may report the following chronic, nonspecific constitutional complaints: Fever, Fatigue, lethargy, Loss of appetite, Weight loss, Conjunctivitis, Optic nerve vasculitis, Retinal artery occlusion, Nasolacrimal duct occlusion, Chronic sinusitis, Rhinitis, Epistaxis, otitis media, Cough, Hemoptysis, Chest discomfort, Dyspnea, Atelectasis, decreased breath sounds, Myalgia’s, Arthralgia’s, Palpable purpura or skin ulcers etc.²

Abbreviations:

ANCA: anti-neutrophil cytoplasmic antibody

c-ANCA: cytoplasmic anti-neutrophil cytoplasmic antibody

CRP: C-reactive protein

ESR: erythrocyte sedimentation rate

GPA: granulomatosis with polyangiitis

MPO-ANCA: myeloperoxidase anti-neutrophil cytoplasmic antibody p-ANCA: perinuclear anti-neutrophil cytoplasmic antibody PR3-ANCA: proteinase 3 anti-neutrophil cytoplasmic antibody

Case reports:

1. Patient information:

Mr. Nigel Reynolds, 55 years male, diagnosed with Wagener’s granulomatosis in 2009 and was treated with Endoran pulse and steroids followed by AZA with Septrum and isoniazide prophylaxis till Sep, 2013. As a surgical intervention Lobectomy was done after which he developed broncho pleural fistula for which pneumonectomy of right lung was performed in 2014. Broncho pleural fistula persisted and had episodes of sclerosis about one year ago. Since one month he developed kin abnormality, flitting arthritis, scleritis (right side). On admission his blood tests showed increase in ESR and CRP and ANCA strongly positive. With all evidences of Wagner’s granulomatosis started on Prednisolone 20mg OD, for 2 days and decided to start longer term strategy for treatment and to rule out possibilities of infections for the future plan of action.

At this point, a positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) test and associated proteinase 3 ANCA (PR3-ANCA) levels (744.5U/ml) were received, suggesting a diagnosis of acute GPA. Our patient was reexamined in detail with specific attention to his history and physical examination features relevant to a GPA diagnosis. A thorough history revealed an active, healthy lifestyle without any significant stressors or past illnesses.

Following the diagnosis of GPA, our patient was immediately treated with methyl prednisone pulse therapy, and after several days intravenous (IV) cyclophosphamide was added. Relevant imaging tests and biopsies were carried out. Chest computed tomography (CT) imaging demonstrated multiple nodules. He was continuously monitored through complete blood count (CBC), electrolyte, renal function, and CRP testing. Despite dealing with sequelae of the acute GPA, he has remained in remission from GPA.

2. Diagnostic tests:

· Urine tests to detect protein and red blood cells in the urine

· X-ray tests of the chest and sinuses which detect abnormalities resulting from lung and sinus inflammation.

· Blood tests to detect the abnormal inflammation include the sedimentation rate and C-reactive protein.

· Anti-neutrophil cytoplasmic antibody (ANCA) test, which is commonly elevated when the disease is active.

· Biopsy of tissue eg; an open lung biopsy or a kidney biopsy

Routine laboratory tests results may include the following:

· Abnormal kidney function tests and urinalysis in patients with renal involvement

· Rheumatoid factor is positive in a low titer in two thirds of patients

· CBC: Mild normochromic normocytic anemia is present in 50% of patients; leukocytosis is common, with a neutrophil predominance

· Elevated inflammatory markers (ESR, CRP)

Anti-neutrophil cytoplasmic antibody (ANCA) testing:

· Cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) directed against PR3 is most specific for GPA

· Some patients with GPA express perinuclear-staining ANCA (p-ANCA) specific for myeloperoxidase (MPO)

· Combining immunofluorescence and ELISA enhances the sensitivity and specificity of a diagnosis of an ANCA-associated vasculitis (AAV)

Chest radiography and CT scanning:

· The most common radiologic findings are single or multiple nodules and masses

· Nodules are typically diffuse, and approximately 50% are cavitated

· Diffuse alveolar opacities, atelectasis, and obstructive pneumonia caused by bronchial stenosis may also be seen

· Findings on CT scans include consolidation, patchy or diffuse ground-glass opacities, or both

· Additional CT scan findings include stenoses of the larynx or tracheobronchial tree, bronchial wall thickening, bronchiectasis, pleural thickening or effusion, and lymphadenopathy

Other studies:

· Sinus CT scanning: The radiographic test of choice to evaluate sinus disease

· Pulmonary testing: Spirometry, plethysmography, and diffusing capacity should be performed as soon as possible to identify abnormalities and provide a baseline

· Bronchoscopy: Helpful in the evaluation of alveolar hemorrhage, infection, airway disease, and endobronchial lesions

· Biopsy: The diagnosis of GPA is generally confirmed with tissue biopsy from a site of active disease; renal and lung biopsies are most specific for GP

Results of tests done on our patient:

Bone density test done which showed osteoporosis of the spine, neck and other areas of the body.

Blood chemistry reports:

· RBS 122 mg/dl

· SGOT 34U/L

· SGPT 52 U/L

· BUN 55mg/dl

· Creatinine 1.2 mg/dl

· Sodium 135mmoL/L

· Pottasium 4.4 mmoL/L

· Chloride 96mmoL/L Hematology:

· Hemoglobin 9.0 gm/dl

· Total Leucocyte count 15,980/cumm

· Neutrophils 86 %

· Lymphocytes 10 %

· Platelet count 220

4. Findings and Patient outcome:

1. Review the etiology:

What causes Wegener's granulomatosis, or GPA is unknown. It appears to develop when an initial inflammation-causing event provokes an abnormal immune system reaction. This leads to inflamed and constricted blood vessels and granulomas, or inflammatory tissue masses. When a relapse occurs, it is sometimes due to an infection. Other contributory factors may be environmental toxins, a genetic predisposition, or a combination of both.¹

The pathologic hallmarks of GPA are vasculitis of the small- to medium-sized vessels, "geographic" necrosis, and granulomatous inflammation, particularly in the airways. The initial pathologic lesion is that of the granuloma believed to be caused by cellular immune processes.

Environmental exposures, including respiratory tract infections, have been implicated as inciting factors for granuloma formation. A better understanding of the progression from granuloma to vasculitis may shed light on the possible etiology and pathogenesis of GPA. It is probable that a complex interaction exists between the environment and host factors, many of which are genetically determined. Cellular immune processes are also involved in tissue injury owing to the inflammatory cascade.²

GPA is slightly more common in men, with a male-to-female ratio of 1.5:1. The onset of GPA may occur at any age, although patients typically present at age 35-55 years and is rare in childhood.

2. Pathophysiology:

Inflammation with granuloma formation against a nonspecific inflammatory background is the classical tissue abnormality in all organs affected by GPA.

It is now widely presumed that the anti-neutrophil cytoplasmic antibodies (ANCAs) are responsible for the inflammation in GPA. The typical ANCAs in GPA are those that react with proteinase 3, an enzyme prevalent in neutrophil granulocytes.

In vitro studies have found that ANCAs can activate neutrophils, increase their adherence to endothelium, and induce their degranulation that can damage endothelial cells. This phenomenon could cause extensive damage to the vessel wall, in particular of arterioles.

Complications usually result from a lack of treatment and may include, End-stage renal disease, chronic pulmonary dysfunction, Hearing loss, and Destructive sinus disease, Saddle nose deformities, Perforation of the nasal septum, Proptosis, Blindness, Skin scarring, if sores develop on the skin, Heart attack, if the arteries of the heart are affected.⁴

3. Treatment:

Medications used to treat GPA include high-dose cortisone (prednisone) and the immunosuppressive drug cyclophosphamide (Cytoxan). Recent studies suggest that trimethoprim/sulfamethoxazole (Bactrim) can also be helpful to prevent relapse of disease activity in patients with GPA.

Medical Management:

· Cyclophosphamide with high-dose glucocorticoids (criterion standard)

· Rituximab with high-dose glucocorticoids

· Methotrexate (oral or subcutaneous) with high-dose glucocorticoids, in non–organ-threatening or non– life-threatening GPA

· Plasma exchange may be considered in patients with rapidly progressive renal disease (serum creatinine level >5.65mg/dl) in order to preserve renal function

Maintenance of remission:

· Once induction of remission has occurred, treatment for maintenance of remission should be continued for at least 18 months, often longer

· Azathioprine (2 mg/kg/day) is safer than, and as effective as, cyclophosphamide in maintaining remission

· Methotrexate (20-25 mg weekly, oral or subcutaneous) has been used for the maintenance of remission if the serum creatinine level is less than 1.5 mg/dl

· Leflunomide (20-30 mg/day) is as effective as methotrexate, but it is associated with more adverse effects

Drugs to prevent side effects:

The drugs used to treat granulomatosis with polyangiitis have the potential to cause serious side effects.

· Sulfamethoxazole-trimethoprim (Bactrim, Septra) to prevent lung infections

· Bisphosphonates (Fosamax) to prevent bone loss (osteoporosis) associated with prednisone use

· Folic acid, a synthetic form of the B vitamin folate, to prevent sores and other signs and symptoms associated with the depletion of folate in the body from methotrexate use

Other treatments:

· Plasma exchange also known as plasmapheresis with fresh plasma or albumin. In people who have very serious granulomatosis with polyangiitis, plasmapheresis can help the kidneys recover.

· Kidney transplant with advanced disease to restore normal kidney function.

4. CONCLUSION:

GPA is one of the ANCA-associated vasculitides (AAVs) and has a predilection for the upper and lower respiratory tracts and the kidneys. Persons with severe disease present with significant multisystem manifestations that may involve the lungs, kidneys, and other organs, in addition to the respiratory tract. With aggressive therapy, more than 50% of patients with GPA recover renal function and are able to become dialysis independent. Unfortunately, relapse is common in GPA. Typically, up to half of patients with GPA experience relapse within 5 years. Factors associated with relapse include treatment (< 10 g of cyclophosphamide in the first 6 months, maintaining a high dose of prednisone [>20 mg/day] and goal of 0 dose of glucocorticoids), ANCA status at diagnosis, and target organ involvement (lung involvement, cardiac involvement, renal involvement, chronic nasal carriage of S aureus).⁵

Poorer survival is associated with older age, target organ involvement, and target organ damage. Renal involvement has been consistently shown to confer a poorer prognosis. An absence of renal involvement is associated with a 100% 5-year survival rate, compared with approximately 70% in individuals with renal disease. The most common causes of death in GPA are: Infection, Respiratory and renal failure, Malignancy, Cardiovascular events. The prognosis for granulomatosis with polyangiitis (GPA) depends on which organs are involved, to what degree they are involved, the duration of the disease, and the response to treatment.³

5. REFERENCES:

1. Hoffman GS, Langford CA, Specks U: Granulomatosis with polyangiitis (Wegener’s). Inflammatory Diseases of Blood Vessels, Page 238-251 (Second edition)

2. Langford CA: Clinical features and diagnosis of small-vessel vasculitis. Cleve Clin J Med. 2012, Suppl 3: S3-S7.

3. Patten SF, Tomecki KJ: Wegener’s granulomatosis: cutaneous and oral mucosal disease. J Am AcadDermatol. 1993, 28: 710-718.

4. Vasculitis Clinical Research Consortium. Granulomatosis with Polyangiitis (Wegener’s). Accessed 2/26/2014.

5. GPA/MPA. Introduction to Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA). Accessed 2/26/2014.

Received on 08.06.2017 Modified on 11.07.2017

Int. J. of Advances in Nur. Management. 2018; 6(1): 15-18.

DOI: 10.5958/2454-2652.2018.00004.5

WAGNER’S Granulomatosis

Molly D’Souza (Sr. Nives UMI)